Systems and  methods for delivering therapeutic agents

ABSTRACT

The present embodiments provide systems and methods suitable for delivering a therapeutic agent to a target site. The systems generally comprise a container having first and second regions and a reservoir containing the therapeutic agent. A pressure source having pressurized fluid is in selective fluid communication with at least a portion of the reservoir. An outlet tube is in fluid communication with the reservoir of the container. At least one slot is formed in a lateral surface of the outlet tube at a position between first and second ends of the outlet tube.

PRIORITY CLAIMS

This application is a continuation-in-part of U.S. Utility patentapplication Ser. No. 13/351,524, filed Jan. 17, 2012, which is acontinuation application that claims the benefit of priority under 35U.S.C. §120 of U.S. patent application Ser. No. 12/787,796, filed May26, 2010, which claims priority under 35 U.S.C. §119 to U.S. ProvisionalPatent Application Ser. No. 61/182,463, filed May 29, 2009, each of theforegoing applications are hereby incorporated by reference in theirentireties.

BACKGROUND

The present embodiments relate generally to medical devices, and moreparticularly, to systems and methods for delivering therapeutic agentsto a target site.

There are several instances in which it may become desirable tointroduce therapeutic agents into the human or animal body. For example,therapeutic drugs or bioactive materials may be introduced to achieve abiological effect. The biological effect may include an array oftargeted results, such as inducing hemostasis, sealing perforations,reducing restenosis likelihood, or treating cancerous tumors or otherdiseases.

Many of such therapeutic agents are injected using an intravenous (IV)technique and via oral medicine. While such techniques permit thegeneral introduction of medicine, in many instances it may be desirableto provide localized or targeted delivery of therapeutic agents, whichmay allow for the guided and precise delivery of agents to selectedtarget sites. For example, localized delivery of therapeutic agents to atumor may reduce the exposure of the therapeutic agents to normal,healthy tissues, which may reduce potentially harmful side effects.

Localized delivery of therapeutic agents has been performed usingcatheters and similar introducer devices. By way of example, a cathetermay be advanced towards a target site within the patient, then thetherapeutic agent may be injected through a lumen of the catheter to thetarget site. Typically, a syringe or similar device may be used toinject the therapeutic agent into the lumen of the catheter. However,such a delivery technique may result in a relatively weak stream of theinjected therapeutic agent.

Moreover, it may be difficult or impossible to deliver therapeuticagents in a targeted manner in certain forms, such as a powder form, toa desired site. For example, if a therapeutic powder is held within asyringe or other container, it may not be easily delivered through acatheter to a target site in a localized manner that may also reducepotentially harmful side effects.

SUMMARY

The present embodiments provide systems and methods suitable fordelivering a therapeutic agent to a target site. The systems generallycomprise a container having first and second regions and a reservoircontaining the therapeutic agent. A pressure source having pressurizedfluid is in selective fluid communication with at least a portion of thereservoir. An outlet tube is in fluid communication with the reservoirof the container. At least one slot is formed in a lateral surface ofthe outlet tube at a position between first and second ends of theoutlet tube.

The first end of the outlet tube may be disposed closer to a target siteand the second end of the outlet tube may be disposed proximal to thefirst end, and the at least one slot may be positioned closer to thefirst end than the second end of the outlet tube. In one example, the atleast one slot extends between about 45 and about 270 degrees around aperimeter of the outer tube.

In one embodiment, fluid from the pressure source is directed through afirst region of the container in a direction towards a second region ofthe container. The fluid then is at least partially redirected to urgethe therapeutic agent in a direction from the second region of thecontainer towards the first region of the container and subsequentlytowards the target site.

In one embodiment, an inlet tube may be disposed within the container,such that the fluid from the pressure source flows through the inlettube and into the reservoir of the container. The fluid from the inlettube may be redirected to then flow in a direction from the secondregion of the container towards the first region of the container. Theoutlet tube may be disposed at least partially within the container,wherein fluid exiting the second end of the inlet tube urges thetherapeutic agent into the second end of the outlet tube.

Other systems, methods, features and advantages of the invention willbe, or will become, apparent to one with skill in the art uponexamination of the following figures and detailed description. It isintended that all such additional systems, methods, features andadvantages be within the scope of the invention, and be encompassed bythe following claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention can be better understood with reference to the followingdrawings and description. The components in the figures are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention. Moreover, in the figures, likereferenced numerals designate corresponding parts throughout thedifferent views.

FIG. 1 is a perspective view of a system in accordance with a firstembodiment.

FIG. 2 is a schematic view of the system of FIG. 1 with a portion of ahousing removed.

FIG. 3 is a side-sectional view of the container of the system of FIGS.1-2.

FIG. 4 is a perspective view of a system in accordance with analternative embodiment.

FIG. 5 is a perspective view of a system in accordance with a furtheralternative embodiment.

FIG. 6 is a perspective view of a system in accordance with yet afurther alternative embodiment.

FIG. 7 is a schematic view of the system of FIG. 6 with a portion of ahousing removed.

FIG. 8 is a perspective view of the container of the system of FIGS.6-7.

FIG. 9 is a schematic view of a system in accordance with yet a furtheralternative embodiment with a portion of a housing removed.

FIG. 10 is a perspective view of the container of the system of FIG. 9.

FIG. 11 is a side-sectional view of a portion of a system in accordancewith an alternative embodiment.

FIG. 12 is a side-sectional view of an alternative actuator arrangement.

FIG. 13 is a perspective view of a system in accordance with analternative outlet tube relative to the embodiment of FIG. 1.

FIG. 14 is a side view illustrating a section of the alternative outlettube of FIG. 13.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In the present application, the term “proximal” refers to a directionthat is generally towards a physician during a medical procedure, whilethe term “distal” refers to a direction that is generally towards atarget site within a patient's anatomy during a medical procedure.

Referring now to FIGS. 1-3, a first embodiment of a system suitable fordelivering one or more therapeutic agents is shown. In this embodiment,the system 20 comprises a container 30 that is configured to hold atherapeutic agent 38, and further comprises at least one pressure source68 that is configured to be placed in selective fluid communication withat least a portion of the container 30, to deliver the therapeutic agent38 through a catheter 90 to a target site within the patient, asexplained more fully below.

The system 20 further comprises a housing 22, which is suitable forsecurely holding, engaging and/or covering the container 30, pressuresource 68, catheter 90, and other components described below.Preferably, the housing 22 comprises an upright section 24 that may begrasped by a user and a section 25 for engaging the container 30.Actuators 26 and 28 may be engaged by a user and selectively operated toperform the functions described below.

The container 30 may comprise any suitable size and shape for holdingthe therapeutic agent 38. In FIGS. 1-3, the container 30 comprises agenerally tube-shaped configuration having a first region 31, a secondregion 32, and a reservoir 33 defined by an interior of the container30. A platform 35 may be positioned within the container 30 above acurved end region 34, as best seen in FIG. 3.

The platform 35 preferably forms a substantially fluid tight seal withan inner surface of the container 30, thereby preventing the therapeuticagent 38 that is disposed in the reservoir 33 from reaching an innerportion of the curved end region 34, as shown in FIG. 3. In thisembodiment, the platform 35 comprises an opening 36 though which fluidfrom the pressure source 68 is directed via a u-shaped tube 37 disposedwithin the curved end region 34, as shown in FIG. 3 and explained infurther detail below.

The container 30 may further comprise an inlet tube 40, an outlet tube50, and a cap 60, wherein the cap 60 is configured to be secured to thefirst region 31 of the container 30, as depicted in FIG. 3. The inlettube 40 has first and second ends 41 and 42 with a lumen 43 extendingtherebetween, while the outlet tube 50 has first and second ends 51 and52 with a lumen 53 extending therebetween. The first end 41 of the inlettube 40 is placed in fluid communication with an inlet port 61 formed inthe cap 60, while the first end 51 of the outlet tube 50 is placed influid communication with an outlet port 62 formed in the cap 60, asshown in FIG. 3.

The second end 42 of the inlet tube 40 extends towards the platform 35,and may be coupled to an adapter 14, which may be integral with theplatform 35 or secured thereto. The adapter 44 places the second end 42of the inlet tube 40 in fluid communication with a first end 45 of theu-shaped tube 37, which is disposed within the curved end region 34, asshown in FIG. 3. A second end 46 of the u-shaped tube 37 is in fluidcommunication with the opening 36 in the platform 35.

Accordingly, fluid passed through the inlet port 61 of the cap 60 isdirected through the inlet tube 40, through the u-shaped tube 37, andinto the reservoir 33 via the opening 36. Notably, the u-shaped tube 37effectively changes the direction of the fluid flow by approximately 180degrees, such that the fluid originally flows in a direction from thefirst region 31 of the container 30 towards the second region 32, andthen from the second region 32 back towards the first region 31. In theembodiment of FIGS. 1-3, the first region 31 of the container 30 isdisposed vertically above the second region 32 of the container 30during use, however, it is possible to have different placements of thefirst and second regions 31 and 32 relative to one another, such thatthey are disposed at least partially horizontally adjacent to oneanother.

The second end 52 of the outlet tube 50 may terminate a predetermineddistance above the platform 35, as shown in FIGS. 1-3. While the secondend 52 is shown relatively close to the platform 35 in this embodiment,any suitable predetermined distance may be provided. For example, theoutlet tube 50 may be shorter in length, e.g., about half of the lengthshown in FIGS. 1-3, and therefore, the second end 52 may be spaced apartfurther from the platform 35. In a presently preferred embodiment, thesecond end 52 of the outlet tube 50 is radially aligned with the opening36 in the platform 35, as depicted in FIGS. 1-3. Accordingly, as will beexplained further below, when fluid from the pressure source 68 isdirected through the opening 36 in the platform 35, the fluid and thetherapeutic agent 38 within the reservoir 33 may be directed through theoutlet tube 50, through the outlet port 62, and towards a target site.Alternatively, the outlet tube 50 may be omitted and the therapeuticagent 38 may flow directly from the reservoir 33 into the outlet port62. Other variations on the container 30 and outlet port 62 may be foundin U.S. patent application Ser. No. 12/633,027, filed Dec. 8, 2009,which is hereby incorporated by reference in its entirety.

The cap 60 may comprise any suitable configuration for sealinglyengaging the first region 31 of the container 30. In one example, anO-ring 65 is held in place around a circumference of the cap 60 to holdthe therapeutic agent 38 within the reservoir 33. Further, the cap 60may comprise one or more flanges 63 that permit a secure, removableengagement with a complementary internal region of the section 25 of thehousing 22. For example, by rotating the container 30, the flange 63 ofthe cap 60 may lock in place within the section 25.

The inlet and outlet tubes 40 and 50 may be held in place within thecontainer 30 by one or more support members. In the example shown, afirst support member 48 is secured around the inlet and outlet tubes 40and 50 near their respective first ends 41 and 51, as shown in FIG. 3.The first support member 48 may be permanently secured around the inletand outlet tubes 40 and 50, and may maintain a desired spacing betweenthe tubes. Similarly, a second support member 49 may be secured aroundthe inlet and outlet tubes 40 and 50 near their respective second ends42 and 52, as shown in FIGS. 1-3. As will be apparent, greater or fewersupport members may be provided to hold the inlet and outlet tubes 40and 50 in a desired orientation within the container 30. For example, inone embodiment, the second support member 49 may be omitted and just thefirst support member 48 may be provided, or greater than two supportmembers may be used.

In a loading technique, the inlet and outlet tubes 40 and 50 may besecurely coupled to the first support member 48, the second supportmember 49, the platform 35 and the u-shaped tube 37. The platform 35 maybe advanced towards the second region 32 of the empty container 30 untilthe platform rests on a step 47 above the curved end region 35 of thecontainer 30, as shown in FIG. 3. In a next step, a desired quantity ofthe therapeutic agent 38 may be loaded through slits 57 formed adjacentto, or within, the first support member 48, as depicted in FIG. 3.Notably, the container 30 also may comprise measurement indicia 39,which allow a user to determine a quantity of the therapeutic agent 38that is loaded within the reservoir 33 as measured, for example, fromthe top of the platform 35. With the therapeutic agent 38 loaded intothe reservoir 33, the cap 60 may be securely coupled to the first region31 of the container 30, and the container 30 then is securely coupled tothe section 25 of the handle 22 as described above.

The pressure source 68 may comprise one or more components capable ofproducing or furnishing a fluid having a desired pressure. In oneembodiment, the pressure source 68 may comprise a pressurized fluid,such as a liquid or gas. For example, as shown in FIG. 2, the pressuresource 68 may comprise a pressurized fluid cartridge of a selected gasor liquid, such as carbon dioxide, nitrogen, or any other suitable gasor liquid that may be compatible with the human body. The pressurizedfluid cartridge may contain the gas or liquid at a relatively high,first predetermined pressure, for example, around 1,800 psi inside ofthe cartridge. The pressure source 68 optionally may comprise one ormore commercially available components. The pressure source 68 thereforemay comprise original or retrofitted components capable of providing afluid or gas at an original pressure.

The fluid may flow from the pressure source 68 through a pressureregulator, such as regulator valve 70 having a pressure outlet 72, asdepicted in FIG. 2, which may reduce the pressure to a lower, secondpredetermined pressure. Solely by way of example, the secondpredetermined pressure may be in the range of about 30 to about 80 psi,although any suitable pressure may be provided for the purposesdescribed below.

The actuator 26 may be actuated to release the fluid from the pressuresource 68. For example, a user may rotate the actuator 26, whichtranslates into linear motion via a threaded engagement 29 between theactuator 26 and the housing 22, as shown in FIG. 2. When the linearadvancement is imparted to the pressure source 68, the regulator valve70 may pierce through a seal of the pressure cartridge to release thehigh pressure fluid. After the regulator valve 70 reduces the pressure,the fluid may flow from the pressure outlet 72 to an actuation valve 80via tubing 75.

The actuation valve 80 comprises an inlet port 81 and an outlet port 82.The actuator 28, which may be in the form of a depressible button, mayselectively engage the actuation valve 80 to selectively permit fluid topass from the inlet port 81 to the outlet port 82. For example, theactuation valve 80 may comprise a piston having a bore formed thereinthat permits fluid flow towards the outlet port 82 when the actuator 28engages the actuation valve 80. Fluid that flows through the outlet port82 is directed into the inlet port 61 of the cap 60 via tubing 85, andsubsequently is directed into the container 30, as explained above. Itwill be appreciated that any suitable coupling mechanisms may beemployed to secure the various pieces of tubing to the various valvesand ports.

The system 20 further may comprise one or more tube members fordelivering the therapeutic agent 38 to a target site. For example, thetube member may comprise a catheter 90 having a proximal end that may beplaced in fluid communication with the outlet port 62. The catheter 90further comprises a distal end that may facilitate delivery of thetherapeutic agent 38 to a target site. The catheter 90 may comprise aflexible, tubular member that may be formed from one or more semi-rigidpolymers. For example, the catheter may be manufactured frompolyurethane, polyethylene, tetrafluoroethylene,polytetrafluoroethylene, fluorinated ethylene propylene, nylon, PEBAX orthe like. Further details of a suitable tube member are described inU.S. patent Ser. No. 12/435,574 (“the '574 application”), filed May 5,2009, the disclosure of which is hereby incorporated by reference in itsentirety. As explained further in the '574 application, a needlesuitable for penetrating tissue may be coupled to the distal end of thecatheter 90 to form a sharp, distal region configured to pierce througha portion of a patient's tissue, or through a lumen wall to perform atranslumenal procedure.

In operation, the distal end of the catheter 90 may be positioned inrelatively close proximity to the target site. The catheter 90 may beadvanced to the target site using an open technique, a laparoscopictechnique, an intraluminal technique, using a gastroenterology techniquethrough the mouth, colon, or using any other suitable technique. Thecatheter 90 may comprise one or more markers configured to be visualizedunder fluoroscopy or other imaging techniques to facilitate location ofthe distal end of the catheter 90. If desired, the catheter 90 may beadvanced through a working lumen of an endoscope.

When the catheter 90 is positioned at the desired target site, thepressure source 68 may be actuated by engaging the actuator 26. As notedabove, the pressurized fluid may flow from the pressure source 68through a regulator valve 70 and be brought to a desired pressure andrate. The fluid then flows through the tubing 75, and when the actuator28 is selectively depressed, the fluid flows through the valve 80 andthrough the tubing 85 towards the container 30. The fluid is thendirected through the inlet port 62, through the inlet tube 40 within thecontainer 30, and through the u-shaped tube 37. At this point, theu-shaped tube effectively changes the direction of the fluid flow.Regulated fluid then flows through the opening 36 in the platform 35 andurges the therapeutic agent 38 through the outlet tube 50. The fluid andthe therapeutic agent 38 then exit through the first end 51 of theoutlet tube 50, through the outlet port 62 of the cap 60, and throughthe catheter 90, thereby delivering the therapeutic agent 38 to thetarget site at a desired pressure.

Optionally, a control mechanism may be coupled to the system 20 tovariably permit fluid flow into and/or out of the container 30 at adesired time interval, for example, a predetermined quantity of fluidper second. In this manner, pressurized fluid may periodically flow intoor out of the container 30 periodically to deliver the therapeutic agent38 to a target site at a predetermined interval or otherwise periodicbasis.

The system 20 may be used to deliver the therapeutic agent 38 in a widerange of procedures and the therapeutic agent 38 may be chosen toperform a desired function upon ejection from the distal end of thecatheter 90. Solely by way of example, and without limitation, theprovision of the therapeutic agent 38 may be used for providinghemostasis, closing perforations, performing lithotripsy, treatingtumors and cancers, treat renal dialysis fistulae stenosis, vasculargraft stenosis, and the like. The therapeutic agent 38 can be deliveredduring procedures such as coronary artery angioplasty, renal arteryangioplasty and carotid artery surgery, or may be used generally fortreating various other cardiovascular, respiratory, gastroenterology orother conditions. The above-mentioned systems also may be used intransvaginal, umbilical, nasal, and bronchial/lung related applications.

For example, if used for purposes of hemostasis, thrombin, epinephrine,or a sclerosant may be provided to reduce localized bleeding. Similarly,if used for closing a perforation, a fibrin sealant may be delivered toa localized lesion. In addition to the hemostatic properties of thetherapeutic agent 38, it should be noted that the relatively highpressure of the fluid and therapeutic agent, by itself, may act as amechanical tamponade by providing a compressive force, thereby reducingthe time needed to achieve hemostasis.

The therapeutic agent 38 may be selected to perform one or more desiredbiological functions, for example, promoting the ingrowth of tissue fromthe interior wall of a body vessel, or alternatively, to mitigate orprevent undesired conditions in the vessel wall, such as restenosis.Many other types of therapeutic agents 38 may be used in conjunctionwith the system 20.

The therapeutic agent 38 may be delivered in any suitable form. Forexample, the therapeutic agent 38 may comprise a powder, liquid, gel,aerosol, or other substance. Advantageously, the pressure source 68 mayfacilitate delivery of the therapeutic agent 38 in any one of theseforms.

The therapeutic agent 38 employed also may comprise an antithrombogenicbioactive agent, e.g., any bioactive agent that inhibits or preventsthrombus formation within a body vessel. Types of antithromboticbioactive agents include anticoagulants, antiplatelets, andfibrinolytics. Anticoagulants are bioactive materials which act on anyof the factors, cofactors, activated factors, or activated cofactors inthe biochemical cascade and inhibit the synthesis of fibrin.Antiplatelet bioactive agents inhibit the adhesion, activation, andaggregation of platelets, which are key components of thrombi and playan important role in thrombosis. Fibrinolytic bioactive agents enhancethe fibrinolytic cascade or otherwise aid in dissolution of a thrombus.Examples of antithrombotics include but are not limited toanticoagulants such as thrombin, Factor Xa, Factor VIIa and tissuefactor inhibitors; antiplatelets such as glycoprotein IIb/IIIa,thromboxane A2, ADP-induced glycoprotein Hb/IIIa, and phosphodiesteraseinhibitors; and fibrinolytics such as plasminogen activators, thrombinactivatable fibrinolysis inhibitor (TAFI) inhibitors, and other enzymeswhich cleave fibrin.

Additionally, or alternatively, the therapeutic agent 38 may includethrombolytic agents used to dissolve blood clots that may adverselyaffect blood flow in body vessels. A thrombolytic agent is anytherapeutic agent that either digests fibrin fibers directly oractivates the natural mechanisms for doing so. Examples of commercialthrombolytics, with the corresponding active agent in parenthesis,include, but are not limited to, Abbokinase (urokinase), AbbokinaseOpen-Cath (urokinase), Activase (alteplase, recombinant), Eminase(anitstreplase), Retavase (reteplase, recombinant), and Streptase(streptokinase). Other commonly used names are anisoylatedplasminogen-streptokinase activator complex; APSAC; tissue-typeplasminogen activator (recombinant); t-PA; rt-PA.

In one example, the therapeutic agent 38 comprises a hemostasis powdermanufactured by TraumaCure, Inc. of Bethesda, Md. However, while a fewexemplary therapeutic agents 38 have been described, it will be apparentthat numerous other suitable therapeutic agents may be used inconjunction with the system 20 and delivered through the catheter 90.

Advantageously, the system 20 permits localized delivery of a desiredquantity of the therapeutic agent 38 at a desired, regulated pressure.Since the distal end of the catheter 90 may be placed in relativelyclose proximity to a target site, the system 20 provides significantadvantages over therapeutic agents delivered orally or through an IVsystem and may reduce accumulation of the therapeutic agent 38 inhealthy tissues, thereby reducing side effects. Moreover, the deliveryof the therapeutic agent 38 to the target site is performed in arelatively fast manner due to the relatively high pressure of the fluid,thereby providing a prompt delivery to the target site compared toprevious devices.

Further, if an optional needle is employed at the distal end of thecatheter 90, as explained in the '574 application, the system 20advantageously may be used to both perforate tissue at or near a targetsite, then deliver the therapeutic agent 38 at a desired pressure in themanner described above. For example, the needle may comprise anendoscopic ultrasound (EUS) needle. Accordingly, in one exemplarytechnique, a sharpened tip of the needle may be capable of puncturingthrough an organ or a gastrointestinal wall or tissue, so that thetherapeutic agent 38 may be delivered at a predetermined pressure invarious bodily locations that may be otherwise difficult to access. Oneor more delivery vehicles, such as an endoscope or sheath, may beemployed to deliver the catheter 90 to a target site, particularly ifthe distal end of the catheter 90 comprises the optional needle.

Referring now to FIGS. 4-5, alternative systems 20′ and 20″ are similarto the system 20 of FIGS. 1-3, with main exceptions noted below. In FIG.4, the alternative system 20′ comprises an inlet tube 40′ having aJ-shaped curvature 93 that causes a second end 42′ of the inlet tube 40′to direct fluid flow in a substantially opposing direction relative tothe first end 41 of the inlet tube 40′. In use, fluid from the pressuresource 68 flows through the first end 41 of the inlet tube 40′, throughthe J-shaped curvature 93 and exits the second end 42′, therebydirecting the therapeutic agent 38 (not shown in FIG. 4) into the outlettube 50 for delivery to a target site via the catheter 90, as generallyexplained above. In this embodiment, the platform 35 may be omitted andthe therapeutic agent 38 may settle on a lower region of the reservoir33. Measurement indicia 39′ may measure a quantity of the therapeuticagent 38 from the lower region of the reservoir 33.

In the embodiment of FIG. 4, as well as FIGS. 1-3, a filter may coverthe second end 52 of the outlet tube 50. The filter may be sized toensure that only relatively small particles of the therapeutic agent 38enter into the outlet tube 50, thereby reducing the risk of clogging. Ifrelatively large particles become present in the reservoir 33, the fluidfrom the pressure source 68 entering into the container may break up thelarger particles until they are small enough to pass through the filterand into the outlet tube 50.

In FIG. 5, the alternative system 20″ comprises an inlet tube 40″ havinga curvature 94 that directs fluid into a flow assembly 95. The flowassembly 95 has an inlet 96 comprising at least one bore configured forfluid communication with the second end 42″ of the inlet tube 40″. Theflow assembly 95 further comprises an outlet 98 that is coupled to, andin fluid communication with, the second end 52 of the outlet tube 50. Atleast one opening 97 is formed in a lateral surface of the flow assembly95 between the inlet 96 and the outlet 98, wherein the openings 97 aresized to permit suctioning of the therapeutic agent 38 therethrough. Theopenings 97 may comprise slits, as generally depicted, or alternativelycircular bores or other shapes. In use, fluid from the pressure source68 flows through the first end 41 of the inlet tube 40″, through thecurvature 94 and the second end 42″, and into the flow assembly 95 viathe inlet 96. The fluid thereby directs the therapeutic agent 38 withinthe reservoir 33 into the outlet tube 50, via the openings 97, fordelivery to a target site via the catheter 90.

In particular, as fluid from the pressure source 68 passes from theinlet 96 to the outlet 98, a localized low pressure system will beprovided in the vicinity of the openings 97 in accordance withBernoulli's principle of fluid dynamics. The low pressure system formedby the presence of the pressurized fluid passing through the flowassembly 95 will form a strong suction force when it passes by theopenings 97. As a result, the therapeutic agent 38 may be suctioned outof the reservoir 33, through the openings 97 and through the outlet 98and outlet tube 50. Notably, the slits or other openings may be sized toensure that only relatively small particles of the therapeutic agent 38enter into the outlet tube 50, thereby reducing the risk of clogging.

Referring now to FIGS. 6-8, a system 120 according to an alternativeembodiment is described. The system 120 comprises a housing 122, whichis suitable for securely holding, engaging and/or covering thecomponents described below. A user may hold the system 120 during use bygrasping an upright support 125 and/or an outer surface of a container130. Actuators 126 and 128, which are similar to actuators 26 and 28above, may be engaged by a user and actuated to perform the functionsdescribed below.

The container 130 may comprise any suitable size and shape for holdingthe therapeutic agent 38 described above (not shown in FIGS. 6-8 forillustrative purposes). The container 130 has a first region 131 and asecond region 132. An upper cap 160 may securely engage the first region131, while a lower cap 165 may securely engage the second region 132,thereby holding the therapeutic agent 38 within a reservoir 133.Measurement indicia 139 are provided to determine a quantity of thetherapeutic agent 38 within the reservoir 133.

In this embodiment, an outlet tube 150 having first and second ends 151and 152 is positioned within the container 130. The second end 152 ofthe tube 150 terminates a predetermined distance above an upper surface168 of the lower cap 165, as shown in FIGS. 6-8. Further, the second end152 of the outlet tube 150 may be aligned with an opening 166 in theupper surface 168 of the lower cap 165, as depicted in FIGS. 6 and 8.

The system 120 further comprises at least one linkage 177 having firstand second ends 178 and 179. The first end 178 of the linkage 177 iscoupled to the actuator 128, while the second end 179 of the linkage 177is coupled to the valve 80. Accordingly, when the actuator 128 isdepressed, the valve 80 may be selectively actuated. The container 130may comprise a groove 137, as best seen in FIG. 8, for accommodating thelinkage 177. The upper and lower caps 160 and 165 also may comprisecorresponding grooves 162 and 167, respectively, for accommodating thelinkage 177. It will be apparent that any number of linkages may beused, and their positioning within the housing 122 may be varied, asneeded, to impart a desired motion from the actuator 128 to selectivelyactuate the valve 80.

Optionally, an orientation device 193 may be used for indicating avertical orientation of the container 130. The orientation device 193may be formed integrally with the housing 122, or coupled to an exteriorsurface of the housing 122. The orientation device 193 may comprise acaptive liquid, ball, arrow or other member, or an electronic display,which provides an indication of the vertical orientation of thecontainer 130. Therefore, when the system 120 is held in a user's hand,the user may determine whether the container 130 is oriented vertically,which may enhance flow of the therapeutic agent 38 and otherfunctionality. Notably, the orientation device 193 shown in FIGS. 6-7also may be used in the embodiments of FIGS. 1-5 and 8-9.

Operation of the system 120 is similar to the operation of the system 20described above. After the catheter 90 is positioned at a desiredlocation, the pressure source 68 may be actuated by engaging theactuator 126. As noted above, the pressurized fluid may flow through aregulator valve 70 and be brought to a desired pressure and rate. Thefluid then flows through the tubing 75, and when the actuator 28 isselectively actuated, the fluid flows through the valve 80 and throughthe tubing 85 towards the container 130. Regulated fluid then flowsthrough the opening 166 within the lower cap 165, into the reservoir133, and urges the therapeutic agent 38 through the outlet tube 150 in adirection from the second end 152 towards the first end 151. The fluidand the therapeutic agent 38 then exit through the first end 151 of theoutlet tube 150, through the opening 161 of the upper cap 160, andthrough the catheter 90, which is in fluid communication with theopening 161. Accordingly, the therapeutic agent 38 is delivered to thetarget site at a desired interval and pressure.

Referring now to FIGS. 9-10, a system 220 according to a furtheralternative embodiment is described. The system 220 comprises a housing222, which is suitable for securely holding, engaging and/or coveringthe components described below, A user may hold the system 220 duringuse by grasping a generally upright support 225. Actuators 226 and 228,which are similar to actuators 26 and 28 above, may be engaged by a userand actuated to perform the functions described below.

In this embodiment, an alternative container 230 comprises a reservoir233 for holding the therapeutic agent 38 described above (not shown inFIGS. 9-10 for illustrative purposes). The container 230 has a firstregion 231 and a second region 232. Measurement indicia 239 are providedto determine a quantity of the therapeutic agent 38 within the reservoir233.

In this embodiment, the second region 232 of the container 230 issecurely coupled to a lower cap 234. The lower cap 234 comprises aninlet port 243, which is in fluid communication with an opening 236formed in an upper surface 235 of the lower cap 234. A flexible u-shapedtube 237 may be coupled between the inlet port 243 and the opening 236to provide fluid communication therebetween, as depicted in FIG. 9.

The system 220 further comprises at least one linkage 277 having firstand second ends 278 and 279. The first end 278 of the linkage 277 iscoupled to the actuator 228, while the second end 279 of the linkage 277may be pivotable about an inner element of the housing 222. For example,the second end 279 may comprise a bore, as shown in FIG. 9, which may besecured around a prong (not shown) extending within the housing 222,thereby allowing the second end 279 to pivot around the prong.Accordingly, when the actuator 228 is depressed, a central region of thelinkage 277 may engage the valve 80 to selectively actuate the valve andpermit flow therethrough. As will be apparent, any number of linkagesmay be used, and their positioning within the housing 222 may be varied,as needed, to impart a desired motion from the actuator 228 toselectively actuate the valve 80.

Operation of the system 220 is similar to the operation of the system 20described above. After the catheter 90 is positioned at a desiredlocation, the pressure source 68 may be actuated by engaging theactuator 226. As noted above, the pressurized fluid may flow through aregulator valve 70 and be brought to a desired pressure and rate. Thefluid then flows through the tubing 75, and when the actuator 228 isselectively actuated, the fluid flows through the valve 80 and throughthe tubing 85. Fluid then flows through the inlet port 243, through theu-shaped tube positioned within the lower cap 234, through the opening236 and into the reservoir 233. Fluid entering the reservoir 233 thenurges the therapeutic agent 38 through an outlet port 261 at the firstregion 231 of the container 230. The first region 231 may comprise acurve or taper 249 to direct the fluid and the therapeutic agent 38through the opening 261. Subsequently, the fluid and the therapeuticagent 38 flow through the catheter 90, which is in fluid communicationwith the opening 261, thereby delivering the therapeutic agent 38 to thetarget site at a desired pressure.

As noted above, in alternative embodiments the outlet tubes 50 and 150of FIGS. 1-5 and 6-8, respectively, may be omitted. Therefore, fluidentering into the reservoirs 33 and 133 may urge the therapeutic agent38 in a direction through outlet port in the caps 60 and 160. A taper orcurve may be provided to guide the therapeutic agent 38 out of thecontainers 30 and 130.

Referring to FIG. 11, in an alternative embodiment, an outlet tube 350has a first end 351 that is coupled to an outlet port 362 formed in adistal tip of the housing 322. The outlet port 362 has proximal anddistal regions 363 and 364, whereby the proximal region 363 isconfigured to securely engage the first end 351 of the outlet tube 350,and the distal region 364 is configured to be coupled to the catheter 90of FIGS. 1-2. A luer-type connection may be provided. Advantageously, bydisposing the outlet tube 350 near the distal tip of the housing, andexposed to a user via a luer-type connection, a physician may easilyexchange the catheter 90 during a procedure, for example, if thecatheter 90 becomes occluded.

Further, FIG. 11 depicts an alternative connection of a container 330 tothe housing 322. The container 330 is similar to the container 30described above, but in the embodiment of FIG. 11, a cap of thecontainer 330 comprises a flanged region 363 having an O-ring 365disposed therein, wherein the flanged region 363 is configured to besecured between upper and lower internal stops 388 and 389 of thehousing 322. In this manner, the flanged region 363 of the cap may beheld in place without the ability to be removed, thereby permanentlysecuring the container 330 to the handle 322 and eliminating theopportunity for the container 330 to be reusable. Notably, otherfeatures of the cap of FIG. 11 that are not shown may be provided in amanner similar to the cap 60 of FIG. 3, such as the inlet port 61.

Referring to FIG. 12, an alternative actuator 426 is provided, which isgenerally similar to the actuator 26 of FIGS. 1-2, with a main exceptionthat there is provided a lower handle portion 427 and a generallyupright portion 428 that extends vertically within the housing 422 andupwards beyond a portion of a regulator valve 70. An upper region of thegenerally upright portion 428 comprises threading 429, which isconfigured to engage threading on an outer surface of the regulatorvalve 70.

In use, a user may rotate the lower handle portion 427 of the actuator426, which translates into linear motion relative to the regulator valve470 via the threaded engagement 429. When the linear advancement isimparted to a pressure source 468 in a chamber, the regulator valve 470may pierce through a seal of the pressure cartridge to release the highpressure fluid. After the regulator valve 470 reduces the pressure, thefluid may flow from the pressure outlet 72 to an actuation valve 80 viatubing 75, in the manner explained in FIG. 2 above. Optionally, a safetyledge or interference may be provided on the housing 422 to prevent theactuator 426 from becoming disengaged, which could otherwise allow thepressure cartridge to be ejected from the device.

Referring now to FIGS. 13-14, a system 20′ for delivering a therapeuticagent is similar to system 20 of the embodiment of FIGS. 1-3, with amain exception that an alternative outlet tube 50′ comprises at leastone slot 55 formed in a lateral surface of the outlet tube 50′. The slot55 is formed in the lateral surface at a location between the first andsecond ends 51 and 52 of the outlet tube 50′. The slot 55 provides anarea of communication between the lumen 53 (shown in FIG. 3 above) ofthe outlet tube and the reservoir 33 defined by an interior of thecontainer 30′.

In one embodiment, the slot 55 extends between about 45 and about 270degrees around a perimeter of the outlet tube 50′, as depicted in FIGS.13-14. In one example, the slot 55 may be positioned at a locationcloser to the first end 51 than the second end 52, as depicted in FIG.13. Further, while one slot 55 is shown in FIGS. 13-14, it is possiblethat multiple slots may be formed in a lateral surface of the outlettube 50′, at locations that are axially spaced apart and/orcircumferentially offset from the slot 55 depicted in FIG. 13. Thelocation of the slot 55 that is depicted in FIG. 13 is not intended tobe limiting.

Advantageously, the inventor has surprisingly discovered that theprovision of the at least one slot 55 may reduce the incidence of thedevice “burping” the therapeutic agent 38 after the actuator 28 isdisengaged by the operator. Furthermore, the provision of the slot 55may reduce the amount of the therapeutic agent 38 that is left in thecatheter 90 that can cause the catheter 90 to clog when it is in contactwith blood.

More specifically, when the actuator 28 is engaged by the operator, thefluid from the pressure source 68 is allowed to enter the reservoir 33holding the therapeutic agent 38 to enable delivery of the therapeuticagent 38 to a target site, as described above. It has been discoveredthat some pressure builds up in the reservoir 33 when the actuator 28 isengaged. When the operator disengages the actuator 28, there is stillsome pressure in the reservoir 33. In the absence of the slot 55, thetherapeutic agent 38 can fall to the bottom of the reservoir 33 due togravity, and then the pressurized fluid from regions above within thereservoir 33 may push a “burp” of the therapeutic agent 38 from thedevice as the fluid pressure is reduced. It has been found that this canleave some of the therapeutic agent 38 within the catheter 90, which cancause clogging. Moreover, an operator may unexpectedly find that some ofthe therapeutic agent 38 is still being deployed from the catheter 90,even after they have disengaged actuation of the actuator 28.

By placing the at least one slot 55 in a lateral surface of the outlettube 50′, the aforementioned potential drawbacks can be avoided. Forexample, in an embodiment in which the slot 55 is positioned closer tothe first end 51 than the second end 52, i.e., higher up when used in agenerally vertical orientation as depicted in FIG. 13, then instead offorcing the therapeutic agent 38 that has settled down in the reservoir33 out of the catheter 90 when some pressure remains in the reservoir33, the pressurized fluid itself can exit the reservoir 33 via the slot55 near the top of the outlet tube 50′. This action has been found toeffectively purge the catheter 90 with substantially only thepressurized fluid, thereby reducing the instance of “burping” with thetherapeutic agent 38 and catheter clogging by the therapeutic agent 38.

It will be appreciated that while the at least one slot 55 has beenshown as being disposed in a lateral surface of the outlet tube 50′ in amodified version of the embodiment of FIGS. 1-3, at least one slot maybe provided in any of the outlet tubes of the alternative embodimentsdescribed herein, i.e., besides the embodiment of FIGS. 1-3.

While various embodiments of the invention have been described, theinvention is not to be restricted except in light of the attached claimsand their equivalents. Moreover, the advantages described herein are notnecessarily the only advantages of the invention and it is notnecessarily expected that every embodiment of the invention will achieveall of the advantages described.

1-20. (canceled)
 21. A system suitable for delivering a therapeuticagent to a target site, the system comprising: a container for holdingthe therapeutic agent, wherein the container comprises first and secondregions, wherein the first region houses the therapeutic agent in apre-delivery state, and wherein the first region comprises an outlet tothe target site, wherein the second region is separated from the firstregion by a platform positioned within the container, the platformforming a substantially fluid tight seal with an inner surface of thecontainer, wherein the therapeutic agent is retained above the platformwhen the system is in a handheld position and there is fluidcommunication through the platform between the first and second regions;and a pressure source having pressurized fluid, the pressure source inselective fluid communication with at least a portion of the container,wherein fluid from the pressure source is directed from the secondregion of the container into the first region of the container via theplatform to urge the therapeutic agent in a direction from the secondregion towards the outlet of the first region and towards the targetsite.
 22. The system of claim 21 further comprising a housing configuredto securely retain the container and the pressure source, wherein thehousing is adapted to be held in a user's hand in the handheld position.23. The system of claim 21 further comprising an orientation device forindicating a vertical orientation of the container when held in a user'shand.
 24. The system of claim 21 further comprising a cap secured to thefirst region of the container, the cap having an inlet port and anoutlet port, wherein the fluid from the pressure source is directedthrough the inlet port of the cap, and wherein the fluid is redirectedwithin the container to urge the therapeutic agent through the outletport of the cap.
 25. The system of claim 21 further comprising an inlettube disposed at least partially within the container, the inlet tubehaving a first end positioned near the first region of the container anda second end positioned near the second region of the container, whereinthe fluid from the pressure source flows through the inlet tube in thedirection from the first region to the second region.
 26. The system ofclaim 25 wherein the second end of the inlet tube comprises at least a90 degree curvature to redirect fluid flow in a direction from thesecond region of the container towards the first region of thecontainer.
 27. The system of claim 25 further comprising a u-shaped tubecoupled to the second end of the inlet tube, wherein the u-shaped tubeis configured to redirect fluid flow in a direction from the secondregion of the container towards the first region of the container. 28.The system of claim 25 further comprising an outlet tube disposed atleast partially within the container, the outlet tube having first andsecond ends, wherein fluid exiting the second end of the inlet tubeurges the therapeutic agent into the second end of the outlet tube andtowards the first end of the outlet tube.
 29. The system of claim 28wherein the second end of the outlet tube is spaced away from the secondend of the inlet tube.
 30. The system of claim 28 further comprising aflow assembly having an inlet, and outlet, and at least one openingdisposed therebetween, wherein the inlet of the flow assembly is coupledto the second end of the inlet tube, the outlet of the flow assembly iscoupled to the second end of the inlet tube, and the at least oneopening is sized to receive the therapeutic agent when fluid passesbetween the inlet and the outlet of the flow assembly.
 31. The system ofclaim 21 further comprising a pressure regulator valve disposed betweenthe pressure source and the container.
 32. The system of claim 21wherein the therapeutic agent comprises a powder.